1. Field of the Invention
The present invention relates to assays for ghrelin O-acyltransferase activity and, more particularly, to a substrate and assay for detecting ghrelin modification by ghrelin O-acyltransferase.
2. Description of the Related Art
The ghrelin-ghrelin O-acyltransferase (GOAT) system has been implicated as a potential target for pharmacologic modulation of a number of disorders, including obesity and diabetes. Ghrelin is a peptide hormone involved in appetite regulation, glucose metabolism, and also potentially learning and memory. To transduce ghrelin-dependent signaling, ghrelin requires octanoylation of its serine 3 residue (GSSFLS . . . ) (SEQ. ID No. 1) to bind and activate its cognate receptor. This acylation is catalyzed by ghrelin O-acyltransferase (GOAT), a member of the MBOAT family of integral membrane enzymes.
With ghrelin impacting multiple physiological pathways, the ghrelin-GOAT system presents an attractive therapeutic target. For example, ghrelin-linked signaling may be involved in various problems, such as obesity, appetite regulation, type II diabetes, and other conditions, as well as involved in learning and memory, depression, and Parkinson's disease. However, the lack of information regarding GOAT structure and catalytic mechanism renders GOAT inhibitor design and optimization difficult.